Most hormones, neurotransmitters or bioactive substances that regulate body functions transmit signals to target cells via guanosine triphosphate-binding protein (hereinafter, “G protein”)-coupled receptors present on cell membranes, whereby their unique functions are exhibited. Such receptors have a seven membrane spanning structure in common and form the G protein-coupled receptor superfamily.
Several hundred different G protein-coupled receptors have already been isolated to date, but some still remain to be isolated. Many orphan receptors with unknown ligands also exist.
Isolation of these receptors and ligands and elucidation of their functions will lead to understanding of their physiological function in the body, and should also permit screening of agonists or antagonists capable of controlling their function, thereby contributing to the development of new pharmaceuticals.
GPR103 (also known as SP9155 or AQ27) is one type of G protein-coupled receptor, and the human GPR103 gene and protein have been isolated by PCR (Polymerase Chain Reaction) using sequence information obtained from an EST and genomic DNA database search based on the amino acid sequence of different G protein-coupled receptors (Non-patent document 1). Also, the amino acid sequence of human GPR103 protein has been disclosed in Patent document 1.
Mouse GPR103 is disclosed in Patent document 2 and Patent document 3. In addition, rat GPR103 is disclosed in Patent document 3.
GPR103 has high homology to orexin, neuropeptide FF and cholecystokinin receptors and was predicted to exhibit similar function to these molecules, but its actual function was unknown. However, Ying Jiang et al. later discovered a peptide that functions as its ligand (Non-patent document 2, Patent document 4), and it has been suggested that it helps to induce secretion of aldosterone in rat adrenal zona glomerulosa (Non-patent document 3).
Candidate compounds for development of therapeutic and diagnostic agents are evaluated by their physiological effects in rodents and primates. This is because candidate compounds exhibit different drug effects in different animal species, and evaluation in primates that are most closely related to humans contributes to efficient development of therapeutic and diagnostic agents with low toxicity.
[Patent document 1] WO0011015
[Patent document 2] WO2002042458
[Patent document 3] Japanese Unexamined Patent Publication No. 2004-000113
[Patent document 4] Japanese Unexamined Patent Publication No. 2001-136981
[Non-patent document 1] Gene, Vol. 275, 83 (2001)
[Non-patent document 2] Journal of Biological Chemistry, Vol. 278, 27652 (2003).
[Non-patent document 3] Journal of Biological Chemistry, Vol. 278, 46387 (2003).